Skip to main content
SpringerLink
Log in

Quality by Design Study of the Direct Analysis in Real Time Mass Spectrometry Response

  • Research Article
  • Published:
Journal of The American Society for Mass Spectrometry

Abstract

A mass spectrometry method has been developed using the Quality by Design (QbD) principle. Direct analysis in real time mass spectrometry (DART-MS) was adopted to analyze a pharmaceutical preparation. A fishbone diagram for DART-MS and the Plackett-Burman design were utilized to evaluate the impact of a number of factors on the method performance. Multivariate regression and Pareto ranking analysis indicated that the temperature, determined distance, and sampler speed were statistically significant (P < 0.05). Furthermore, the Box-Behnken design combined with response surface analysis was then employed to study the relationships between these three factors and the quality of the DART-MS analysis. The analytical design space of DART-MS was thus constructed and its robustness was validated. In this presented approach, method performance was mathematically described as a composite desirability function of the critical quality attributes (CQAs). Two terms of method validation, including analytical repeatability and method robustness, were carried out at an operating work point. Finally, the validated method was successfully applied to the pharmaceutical quality assurance in different manufacturing batches. These results revealed that the QbD concept was practical in DART-MS method development. Meanwhile, the determined quality was controlled by the analytical design space. This presented strategy provided a tutorial to the development of a robust QbD-compliant mass spectrometry method for industrial quality control.

ᅟ

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Hajslova, J., Cajka, T., Vaclavik, L.: Challenging applications offered by direct analysis in real time (DART) in food-quality and safety analysis. TrAC Trends Anal. Chem. 30, 204–218 (2011)

    Article  CAS  Google Scholar 

  2. Glenn, A.H., Asiri, S.G., Facundo, M.F.: Ambient sampling/ionization mass spectrometry: applications and current trends. Anal. Chem. 83, 4508–4538 (2011)

    Article  Google Scholar 

  3. Chen, H.W., Talaty, N.N., Takáts, Z., Cooks, R.G.: Desorption electrospray ionization mass spectrometry for high-throughput analysis of pharmaceutical samples in the ambient environment. Anal. Chem. 77, 6915–6927 (2005)

    Article  CAS  Google Scholar 

  4. Saang’onyo, D.S.: Optimization and validation of direct analysis in real time mass spectrometry (DART-MS) for quantitation of sugars to advance biofuel production. Online Theses and Dissertations, Paper 44 (2011)

  5. Vogt, F.G., Kord, A.S.: Development of quality-by-design analytical methods. J. Pharm. Sci. 100, 797–812 (2011)

    Article  CAS  Google Scholar 

  6. Rozet, E., Lebrun, P., Debrus, B., Boulanger, B., Hubert, P.: Design spaces for analytical methods. TrAC Trends Anal. Chem. 42, 157–167 (2013)

    Article  CAS  Google Scholar 

  7. Schweitzer, M., Pohl, M., Hanna-Brown, M., Nethercote, P., Borman, P., Hansen, G., Smith, K., Larew, J.: Implications and opportunities of applying QbD principles to analytical measurements. Pharm. Technol. 34, 52–59 (2010)

    CAS  Google Scholar 

  8. Nethercote, P., Ermer, J.: Quality by design for analytical methods: implications for method validation and transfer. Pharm. Technol. 36, 74–79 (2012)

    Google Scholar 

  9. Orlandini, S., Pinzauti, S., Furlanetto, S.: Application of quality by design to the development of analytical separation methods. Anal. Bioanal. Chem. 405, 443–450 (2013)

    Article  CAS  Google Scholar 

  10. Piepel, G., Pasquini, B., Cooley, S., Heredia-Langner, A., Orlandini, S., Furlanetto, S.: Mixture-process variable approach to optimize a microemulsion electrokinetic chromatography method for the quality control of a nutraceutical based on coenzyme Q10. Talanta 97, 73–82 (2012)

    Article  CAS  Google Scholar 

  11. Debrus, B., Lebrun, P., Ceccato, A., Caliaro, G., Rozet, E., Nistor, I., Oprean, R., Rupérez, F.J., Barbas, C., Boulanger, B., Hubert, P.: Application of new methodologies based on design of experiments, independent component analysis, and design space for robust optimization in liquid chromatography. Anal. Chim. Acta. 691, 33–42 (2011)

    Article  CAS  Google Scholar 

  12. Ackerman, L.K., Noonan, G.O., Begley, T.H.: Assessing direct analysis in real-time-mass spectrometry (DART-MS) for the rapid identification of additives in food packaging. Food Addit. Contam. A 26, 1611–1618 (2009)

    Article  CAS  Google Scholar 

  13. Lebrun, P., Krier, F., Mantanus, J., Grohganz, H., Yang, M.S., Rozet, E., Boulanger, B., Evrard, B., Rantanen, J., Hubert, P.: Design space approach in the optimization of the spray-drying process. Eur. J. Pharm. Biopharm. 80, 226–234 (2012)

    Article  CAS  Google Scholar 

  14. Rozet, E., Marini, R.D., Ziemons, E., Boulanger, B., Hubert, P.: Advances in validation, risk, and uncertainty assessment of bioanalytical methods. J. Pharm. Biomed. Anal. 55, 848–858 (2011)

    Article  CAS  Google Scholar 

  15. Cela, R., Ordonez, E., Quintana, J.B., Rodil, R.: Chemometric-assisted method development in reversed-phased liquid chromatography. J. Chromatogr. A 1287, 2–22 (2013)

    Article  CAS  Google Scholar 

  16. Awotwe-Otoo, D., Agarabi, C., Faustino, P.J., Habib, M.J., Lee, S., Khan, M.A., Shah, R.B.: Application of quality by design elements for the development and optimization of an analytical method for protamine sulfate. J. Pharm. Biomed. Anal. 62, 61–67 (2012)

    Article  CAS  Google Scholar 

  17. Ma, Y., Gao, H.M., Liu, J., Chen, L.M., Zhang, Q.W., Wang, Z.M.: Identification and determination of the chemical constituents in a herbal preparation, Compound Kushen injection, by HPLC and LC-DAD-MS/MS. J. Liq. Chromatogr. Related Technol. 37, 207–220 (2014)

    Google Scholar 

  18. Jimidar, M., Bourguignon, B., Massart, D.L.: Application of Derringer’s desirability function for the selection of optimum separation conditions in capillary zone electrophoresis. J. Chromatogr. A 740, 109–117 (1996)

    Article  CAS  Google Scholar 

  19. Rozet, E., Ziemons, E., Marini, R.D., Boulanger, B., Hubert, P.: Validation of analytical methods involves in dissolution assays: acceptance limits and decision methodologies. Anal. Chim. Acta. 751, 44–51 (2012)

    Article  CAS  Google Scholar 

  20. Vaclavik, L., Cajka, T., Hrbek, V., Hajslova, J.: Ambient mass spectrometry employing direct analysis in real time (DART) ion source for olive oil quality and authenticity assessment. Anal. Chim. Acta. 645, 56–63 (2009)

    Article  CAS  Google Scholar 

  21. Vaclavik, L., Hrbek, V., Cajka, T., Rohlik, B.A., Pipek, P., Hajslova, J.: Authentication of animal fats using direct analysis in real time (DART) ionization-mass spectrometry and chemometric tools. J. Agric. Food Chem. 59, 5919–5926 (2011)

    Article  CAS  Google Scholar 

  22. Borman, P.J., Chatfield, M.J., Damjanov, I., Jackson, P.: Method ruggedness studies incorporating a risk based approach: a tutorial. Anal. Chim. Acta. 703, 101–113 (2011)

    Article  CAS  Google Scholar 

  23. Zhou, M.S., McDonald, J.F., Fernández, F.M.: Optimization of a direct analysis in real time/time-of-flight mass spectrometry method for rapid serum metabolomic fingerprinting. J. Am. Soc. Mass Spectrom. 21, 68–75 (2010)

    Article  Google Scholar 

  24. Navare, A.T., Mayoral, J.G., Nouzova, M., Noriega, F.G., Fernández, F.M.: Rapid direct analysis in real time (DART) mass spectrometric detection of juvenile hormone Ш and its terpene precursors. Anal. Bioanal. Chem. 398, 3005–3013 (2010)

    Article  CAS  Google Scholar 

  25. Cescut, J., Severac, E., Molina-Jouve, C., Uribelarrea, J.L.: Optimizing pressurized liquid extraction of microbial lipids using the response surface method. J. Chromatogr. A 1218, 373–379 (2011)

    Article  CAS  Google Scholar 

  26. Saang’onyo, D.S., Smith, D.L.: Optimization of direct analysis in real time (DART) linear ion trap parameters for the detection and quantitation of glucose. Rapid Commun. Mass Spectrom. 26, 385–391 (2012)

    Article  Google Scholar 

  27. Li, Y.J., Wang, Z.Z., Bi, Y.A., Ding, G., Sheng, L.S., Qin, J.P., Xiao, W., Li, J.C., Wang, Y.X., Wang, X.: The evaluation and implementation of direct analysis in real time quadrupole time-of-flight tandem mass spectrometry for characterization and quantification of geniposide in Re Du Ning injections. Rapid Commun. Mass Spectrom. 26, 1377–1384 (2012)

    Article  CAS  Google Scholar 

  28. Monks, K., Molnár, I., Rieger, H.J., Bogáti, B., Szabó, E.: Quality by design: multidimensional exploration of the design space in high performance liquid chromatography method development for better robustness before validation. J. Chromatogr. A 1232, 218–230 (2012)

    Article  CAS  Google Scholar 

  29. Monks, K.E., Rieger, H.-J., Molnár, I.: Expanding the term “Design Space” in high performance liquid chromatography (1). J. Pharm. Biomed. Anal. 56, 874–879 (2011)

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge financial support for this research by the National Natural Science Foundation of China (no. 81273992).

Author information

Authors and Affiliations

  1. Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, No. 866 Yuhangtang Road, Hangzhou, 310058, China

    Lu Wang, Teng Chen, Shanshan Zeng & Haibin Qu

Authors
  1. Lu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Teng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shanshan Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Haibin Qu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Haibin Qu.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Figure S-1

Fishbone diagram of the DART-MS method. (JPEG 19 kb)

High resolution image (TIFF 5096 kb)

Figure S-2

Average absolute peak areas of the respective ions (m/z 247, 263, 453, 495, 511, and 527) produced from the sample ionized at various gas temperatures. (JPEG 13 kb)

High resolution image (TIFF 1780 kb)

Figure S-3

The practical design space for Cube showing the simultaneous influence of the ionization temperature, sampler speed, and distance on the modeled response. The critical working points are highlighted. (JPEG 16 kb)

High resolution image (TIFF 1992 kb)

Table S-1

(DOCX 15 kb)

Table S-2

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, L., Chen, T., Zeng, S. et al. Quality by Design Study of the Direct Analysis in Real Time Mass Spectrometry Response. J. Am. Soc. Mass Spectrom. 25, 278–285 (2014). https://doi.org/10.1007/s13361-013-0779-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13361-013-0779-6

Key words

Search

Navigation